title: Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds.
abstract: Mesenchymal stromal/stem cells (MSCs) are considered promising cellular therapeutics in the fields of tissue engineering and regenerative medicine. MSCs secrete high concentrations of immunomodulatory cytokines and growth factors, which exert paracrine effects on infiltrating immune and resident cells in the wound microenvironment that could favorably promote healing after acute injury. However, better spatial delivery and improved retention at the site of injury are two factors that could improve the clinical application of MSCs. In this study, we utilized thiol-ene Michael-type addition for rapid encapsulation of MSCs within a gelatin/poly(ethylene glycol) biomatrix. This biomatrix was also applied as a provisional dressing to full thickness wounds in Sprague-Dawley rats. The three-way interaction of MSCs, gelatin/poly(ethylene glycol) biomatrices, and host immune cells and adjacent resident cells in the wound microenvironment favorably modulated wound progression and host response. In this model we observed attenuated immune cell infiltration, lack of foreign giant cell (FBGC) formation, accelerated wound closure and re-epithelialization, as well as enhanced neovascularization and granulation tissue formation by 7 days. The MSC entrapped in the gelatin/poly(ethylene glycol) biomatrix localized cell presentation adjacent to the wound microenvironment and thus mediated the early resolution of inflammatory events and facilitated the proliferative phases in wound healing.
authors.affiliation: School of Pharmacy, Division of Pharmaceutical Sciences, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA; Quishi Academy for Advanced Studies, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Kedi
authors.initials: K
authors.lastname: Xu
authors.forename: David Antonio
authors.initials: DA
authors.lastname: Cantu
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: Jaehyup
authors.initials: J
authors.lastname: Kim
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Zheng
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.forename: W John
authors.initials: WJ
authors.lastname: Kao
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D018914:Cells, Immobilized / Q000166:cytology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005780:Gelatin / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D011092:Polyethylene Glycols / Q000138:chemical synthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001672:Biocompatible Materials; D005780:Gelatin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D011956:Receptors, Cell Surface; D013438:Sulfhydryl Compounds; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Cell-based therapy; Foreign body response; Inflammation; Macrophages; Mesenchymal stem cells